Ropivacaine

Iupac Name：(2S)-N-(2,6-dimethylphenyl)-1-propylpiperidine-2-carboxamide

Molecular Weight：274.408

Modify Date.: 2022-11-22 17:03

Introduction: Ropivacaine HCl is an anaesthetic agent and blocks impulse conduction in nerve fibres through inhibiting sodium ion influx reversibly. - See more at: http://www.selleckchem.com/products/ropivacaine-hcl.html#sthash.hTK3J8yF.dpuf View more+

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1. Names and Identifiers

1.1 Name: Ropivacaine
1.2 Synonyms: (-)-1-propyl-2',6'-dimethyl-2-piperidylcarboxyanilide (-)-1-Propyl-2',6'-pipecoloxylidide (+-)-ropivacaine hydrochloride (2S)-1-Propyl-2-(2,6-dimethylphenyl)carbamoylpiperidine (2S)-N-(2,6-Dimethylphenyl)-1-propyl-2-piperidinecarboxamide (2S)-N-(2,6-Dimethylphenyl)-1-propyl-2-piperidinecarboxamide hydrochloride hydrate (2S)-N-(2,6-Dimethylphenyl)-1-propylpiperidine-2-carboxamide (2S)-N-(2,6-Dimethylphenyl)-1-propylpiperidine-2-carboxamide hydrochloride hydrate (S)-(-)-1-propyl-2',6'-pipecoloxylidide (S)-(-)-1-propyl-2',6'-pipecoloxylidine hydrochloride monohydrate (S)-(-)-ropivacaine (S)-N-(2，6-Dimethylphenyl)-1-pKIpyl-2-piperidinecarboxamide (S)-N-(2,6-dimethylphenyl)-1-propyl-2-piperidinecarboxamide (S)-N-propylpiperidine-2-carboxylic acid 2,6-dimethylphenyl amide (S)-ROPIVACAINE HCL (S)ROPIVACAINE HY DROCHLORIDE (S)ROPIVACAINE HYDROCHLORIDE (S)-ROPIVACAINE HYDROCHLORIDE (S)-ropivacaine hydrochloride hydrate (S)-ROPIVACAINEHCL (S)-ROPIVACAINEHYDROCHLORIDE 2-Piperidinecarboxamide, N-(2,6-dimethylphenyl)-1-propyl-, (2S)- 2-Piperidinecarboxamide, N-(2,6-dimethylphenyl)-1-propyl-, (2S)-, hydrochloride, hydrate (1:1:1) l-N-n-Propylpipecolic acid-2,6-xylidide MFCD00864425 Naropin Naropine ROPACARAINEHCL Ropivacaine (hydrochloride Monohydrate) Ropivacaine API Ropivacaine HCl Ropivacaine HCl.H2O Ropivacaine hydrochloride ropivacaine hydrochloride hydrate Ropivacaine hydrochloride Monohydrate ROPIVACAINE MESYLATER RopivacaineHcl/MesylateBase Ropivacainehydrochloride S-ROPIVACAINE HCL S-ROPIVACAINE HYDROCHLORIDE S-ROPIVACAINEHCL UNII-7IO5LYA57N UNII-V910P86109

1.3 CAS No.: 84057-95-4

1.4 CID: 175805

1.5 EINECS(EC#): 617-525-1

1.6 Molecular Formula: C17H26N2O (isomer)

1.7 Inchi: InChI=1S/C17H26N2O/c1-4-11-19-12-6-5-10-15(19)17(20)18-16-13(2)8-7-9-14(16)3/h7-9,15H,4-6,10-12H2,1-3H3,(H,18,20)/t15-/m0/s1

1.8 InChkey: ZKMNUMMKYBVTFN-HNNXBMFYSA-N

1.9 Canonical Smiles: CCCN1CCCCC1C(=O)NC2=C(C=CC=C2C)C

1.10 Isomers Smiles: CCCN1CCCC[C@H]1C(=O)NC2=C(C=CC=C2C)C

2. Properties

2.1 Density: 1.044

2.1 Melting point: 144 - 146

2.1 Boiling point: 410.2 °C at 760 mmHg

2.1 Refractive index: 1.55

2.1 Flash Point: 201.9 °C

2.1 Precise Quality: 274.20500

2.1 PSA: 32.34000

2.1 logP: 3.51730

2.1 Appearance: 1

2.1 Storage: Ambient temperatures.

2.2 Physical: Solid

2.3 pKa: 8.16(at 25℃)

2.4 Water Solubility: 2.53e-01 g/L

2.5 StorageTemp: Store in original container in a cool dark place.

3. Use and Manufacturing

3.1 Definition: ChEBI: A piperidinecarboxamide-based amide-type local anaesthetic (amide caine) in which (S)-N-propylpipecolic acid and 2,6-dimethylaniline are combined to form the amide bond.

3.2 GHS Classification: Signal: Danger
GHS Hazard Statements
Aggregated GHS information provided by 30 companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

H302 (16.67%): Harmful if swallowed [Warning Acute toxicity, oral]
H318 (76.67%): Causes serious eye damage [Danger Serious eye damage/eye irritation]
H412 (16.67%): Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

Precautionary Statement Codes
P264, P270, P273, P280, P301+P312, P305+P351+P338, P310, P330, and P501

3.3 Usage: Ropivacaine HCl is an anaesthetic agent and blocks impulse conduction in nerve fibres through inhibiting sodium ion influx reversibly. - See more at: http://www.selleckchem.com/products/ropivacaine-hcl.html#sthash.hTK3J8yF.dpuf

4. Safety and Handling

4.1 Hazard Codes: Xi

4.1 Risk Statements: 36/37/39-26

4.1 Safety Statements: R36/37/38:Irritating to eyes, respiratory system and skin .

4.1 Hazard Declaration: H302

4.1 Caution Statement: P261, P264, P270, P271, P273, P280, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

4.1 WGK Germany: 3

4.1 RTECS: LK8650000

4.1 Specification

The IUPAC name of?this chemical?is?(2S)-N-(2,6-dimethylphenyl)-1-propylpiperidine-2-carboxamide. With the?CAS registry number 84057-95-4,?it is also named as Ropivacaine.?The classification codes are?Anesthetics;?Anesthetics, local;?Central Nervous System Agents;?Central Nervous System Depressants;?Peripheral Nervous System Agents;?Sensory System Agents.?It was developed after bupivacaine was noted to be associated with cardiac arrest, particularly in pregnant women. Ropivacaine was found to have less cardiotoxicity than bupivacaine in animal models.

The other characteristics of this product can be summarized as:?(1)ACD/LogP: 3.11; (2)# of Rule of 5 Violations: 0; (3)ACD/LogD (pH 5.5): 0.94; (4)ACD/LogD (pH 7.4): 2.62; (5)ACD/BCF (pH 5.5): 1; (6)ACD/BCF (pH 7.4): 44.01; (7)ACD/KOC (pH 5.5): 7.96; (8)ACD/KOC (pH 7.4): 380.06; (9)#H bond acceptors: 3; (10)#H bond donors: 1; (11)#Freely Rotating Bonds: 4; (12)Index of Refraction: 1.552; (13)Molar Refractivity: 83.98 cm³; (14)Molar Volume: 262.7 cm³; (15)Polarizability: 33.29×10^-24cm³; (16)Surface Tension: 42 dyne/cm; (17)Enthalpy of Vaporization: 66.25 kJ/mol; (18)Vapour Pressure: 6.13E-07 mmHg at 25°C; (19)Rotatable Bond Count: 4; (20)Tautomer Count: 2; (21)Exact Mass: 274.204513; (22)MonoIsotopic Mass: 274.204513; (23)Topological Polar Surface Area: 32.3; (24)Heavy Atom Count: 20.

Preparation of N-(2,6-Dimethylphenyl)-1-propyl-piperidine-2-carboxamide:?It can be obtaind by the following method.

Uses of N-(2,6-Dimethylphenyl)-1-propyl-piperidine-2-carboxamide: It?is a local anaesthetic drug belonging to the amino amide group.?And it is used for analgesia in surgery,?stages of labor?and postoperatief.?Additionally, it is also sometimes used for infiltration anaesthesia for surgical pain in children.?

People can use the following data to convert to the molecule structure.
1. SMILES:O=C(Nc1c(cccc1C)C)[C@H]2N(CCC)CCCC2?
2. InChI:InChI=1/C17H26N2O/c1-4-11-19-12-6-5-10-15(19)17(20)18-16-13(2)8-7-9-14(16)3/h7-9,15H,4-6,10-12H2,1-3H3,(H,18,20)/t15-/m0/s1.

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5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Acute toxicity - Oral, Category 4

Skin irritation, Category 2

Eye irritation, Category 2

Acute toxicity - Inhalation, Category 4

Hazardous to the aquatic environment, long-term (Chronic) - Category Chronic 3

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Warning
Hazard statement(s)	H302 Harmful if swallowed H315 Causes skin irritation H319 Causes serious eye irritation H332 Harmful if inhaled H412 Harmful to aquatic life with long lasting effects
Precautionary statement(s)
Prevention	P264 Wash ... thoroughly after handling. P270 Do not eat, drink or smoke when using this product. P280 Wear protective gloves/protective clothing/eye protection/face protection. P261 Avoid breathing dust/fume/gas/mist/vapours/spray. P271 Use only outdoors or in a well-ventilated area. P273 Avoid release to the environment.
Response	P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/\u2026if you feel unwell. P330 Rinse mouth. P302+P352 IF ON SKIN: Wash with plenty of water/... P321 Specific treatment (see ... on this label). P332+P313 If skin irritation occurs: Get medical advice/attention. P362+P364 Take off contaminated clothing and wash it before reuse. P305+P351+P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P337+P313 If eye irritation persists: Get medical advice/attention. P304+P340 IF INHALED: Remove person to fresh air and keep comfortable for breathing. P312 Call a POISON CENTER/doctor/\u2026if you feel unwell.
Storage	none
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

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6. Synthesis Route

84057-95-4Total: 2 Synthesis Route

98717-15-8 108 Suppliers

84057-95-4 108 Suppliers

Literatures:
BRIDGE PHARMA, INC. Patent: WO2008/88756 A1, 2008 ; Location in patent: Page/Page column 34 ;
Yield: ~90%

106-94-5 69 Suppliers

27262-40-4 145 Suppliers

84057-95-4 108 Suppliers

Literatures:
L. MOLTENI and C. DEI FRATELLI ALITTI - SOCIETA DI ESERCIZIO S.P.A. Patent: WO2006/133837 A2, 2006 ; Location in patent: Page/Page column 3-4 ;
Yield: ~93%

7. Precursor and Product

precursor:

106-94-5

27262-40-4

98717-15-8

product :

132112-35-7

98717-15-8

8. Other Information

8.0 Uses: (S)-Ropivacaine acts as a local anaesthetic for use during medical procedures. Frequently used in epidural procedures as a labor analgesia

8.1 Pharmacology: This is a single (S–) enantiomer, similar in structure to bupivacaine. S ubstitution of a propyl for the butyl side chain of bupivacaine reduces lipid solubility; this leads to reduced potential for toxicity and also greater separation between sensory and motor blockade. Efficacy is similar, but motor block is reduced compared with equianalgesic doses of racemic bupivacaine.

8.2 Originator: Astra (Sweden)

8.3 Uses: Ropivacaine is a pure S(-)-enantiomer of propivacaine. It is a long-acting amide local anesthetic that has efficacy and potency nearly as high as bupivacaine and levobupivacaine but has lower CNS and cvS toxicity. If there are any differences between bupivacaine and ropivacaine it is the slightly shorter period of activity in spinal and epidural applications and a lowered ability to penetrate large motor nerves. It is the reduced lipophilicity that contributed to the lowered penetration of the motor nerves, combined with its stereoselective properties that allows ropivacaine to have significantly reduced Cvs toxicity compared to bupivacaine (Simpson et al. 2005). Ropivacaine has a diphasic effect on peripheral vasculature-it is vasoconstrictive when injected at a concentration below 0.5 w/v% and there is dilation at concentrations over 1 w/v% (Cederholm et al. 1992).
Ropivacaine HCl is an anaesthetic agent and blocks impulse conduction in nerve fibres through inhibiting sodium ion influx reversibly.
http://www.selleckchem.com/products/ropivacaine-hcl.html

8.4 Definition: ChEBI: A piperidinecarboxamide-based amide-type local anaesthetic (amide caine) in which (S)-N-propylpipecolic acid and 2,6-dimethylaniline are combined to form the amide bond.

8.5 Brand name: Narapin [as hydrochloride] (Astra).

8.6 Biological Functions: Ropivacaine (Naropin) is a recently developed longacting amide-linked local anesthetic. Its duration of action is similar to that of bupivacaine, but it is slightly less potent and requires higher concentrations to achieve the same degree of block. Its primary advantage over bupivacaine is its lesser degree of cardiotoxicity.

8.7 Mechanism of action: Ropivacaine is a member of the amino amide class of local anesthetics and is supplied as the pure S-(- )-enantiomer. Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone.

8.8 Clinical Use: Ropivacaine is a long-acting amide-type local anestheticwith inherent vasoconstrictor activities, so it does not requirethe use of additional vasoconstrictors. It is approved forepidural, nerve block, infiltration, and intrathecal anesthesia.

8.9 Side effects: Reactions to ropivacaine are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs may be associated with excessive plasma levels, which may be due to overdosage, unintentional intravascular injection or slow metabolic degradation.
Check with your doctor or nurse immediately if any of the following side effects occur:
More common
Blurred vision
chest pain or discomfort
confusion
dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
lightheadedness, dizziness, or fainting
slow or irregular heartbeat
sweating
unusual tiredness or weakness
Less common
Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
chills
decrease in frequency or amount of urine
difficulty in passing urine (dribbling)
fever
painful urination
Rare
Absence of or decrease in body movement
agitation
anxiety
https://www.mayoclinic.org/drugs-supplements/ropivacaine-injection-route/side-effects/drg-20065875
https://www.accessdata.fda.gov/

8.10 Dissociation Constants: 8.07

8.11 Livertox Summary: The amide local anesthetics including lidocaine, bupivacaine and ropivacaine are commonly used for pain control during minor surgery or invasive procedures such as biopsies, small excisions or dental work. These local anesthetics have not been linked to serum enzyme elevations, but when given as constant infusions or repeated injections have been occasionally mentioned as possible causes of clinically apparent liver injury.

8.12 Drug Classes: Anesthetics, Local

8.13 Mesh: Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate. (See all compounds classified as Anesthetics, Local.)

8.14 Absorption: Bioavailability is 87%–98% following epidural administration.|Ropivacaine is extensively metabolized in the liver, predominantly by aromatic hydroxylation mediated by cytochrome P4501A to 3-hydroxy ropivacaine. After a single IV dose approximately 37% of the total dose is excreted in the urine as both free and conjugated 3-hydroxy ropivacaine. In total, 86% of the ropivacaine dose is excreted in the urine after intravenous administration of which only 1% relates to unchanged drug.|387?+/- 107 mL/min

8.15 Metabolism: Hepatic|Ropivacaine has known human metabolites that include 3-hydroxy-ropivacaine and PPX.

8.16 Biological Half Life: Approximately 4.2 hours.

8.17 Mesh Entry Terms: 1 Propyl 2',6' pipecoloxylidide

8.18 Use Classification: Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

9. Computational chemical data

Molecular Weight: 274.408g/mol
Molecular Formula: C₁₇H₂₆N₂O
Compound Is Canonicalized: True
XLogP3-AA: null
Exact Mass: 274.204513457
Monoisotopic Mass: 274.204513457
Complexity: 308
Rotatable Bond Count: 4
Hydrogen Bond Donor Count: 1
Hydrogen Bond Acceptor Count: 2
Topological Polar Surface Area: 32.3
Heavy Atom Count: 20
Defined Atom Stereocenter Count: 1
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 1
CACTVS Substructure Key Fingerprint: AAADceB7IAAAAAAAAAAAAAAAAAAAAAAAAAA8QAAAAAAAAAABAAAAHgAQAAAADCjBmAQywIPAAACIAiVSUACCAAAhAAAIiAGIRIgIYDLAkbGUIAhglADIyAcYiEAOAAACAAACAAAAAAQAAAQAAAAAAAAAAA==